Molecular Modeling Studies on the Selectivity of 4-Benzylpiperidine Antagonists for hCCR3

Abstract

Abstract: The “antagonist-bound” three-dimensional models of the hCCR3 and hCCR1 receptors were constructed by homology modeling, using the X-ray structure of bovine rhodopsin as the template, and refined with molecular modeling and molecular dynamics(MM/MD) methods. We also carried out an automated docking of several 1,4-disubstituted piperidine antagonists into the hCCR3 and hCCR1 model. The binding hypothesis and the reliability of the hCCR3 model were confirmed by the reasonable correlation between the estimated binding free energy and the experimental -lgIC₅₀ values(r²=0.94). The docking results reveal that the face-to-face van der Waals interaction between piperidine ring and Tyr255 plays an important role on the selectivity of 4-phenzylpiperidine antagonists to hCCR3. Simultaneously, the more hydrophobic of the EL2 in hCCR3 is favorable for the selectivity of 4-phenzylpiperidine antagonists.

Key words: hCCR3, hCCR1, 4-Phenzylpiperidine antagonist, Hydrophobicity, Molecular modeling

TrendMD:

LI Jin-Lian, WANG Jian-Ping, HU Dong-Hua, SHAO Chen, SU Zhong-Min*. Molecular Modeling Studies on the Selectivity of 4-Benzylpiperidine Antagonists for hCCR3[J]. Chem. J. Chinese Universities, 2010, 31(8): 1636.

References

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